NEUROBEHAVIORAL CONSEQUENCES OF PRENATAL TCDD EXPOSURE

产前 TCDD 暴露的神经行为后果

• 批准号: 6017013
• 负责人: Bernard Weiss
• 金额: $ 20.4万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6017013
• 关键词: animal developmental psychology; behavioral /social science research tag; cognition; dioxins; embryo /fetus toxicology; environmental toxicology; gender difference; laboratory rat; motivation; neuroendocrine system; reproductive development; sex behavior

DESCRIPTION: (Adapted from the Investigator's Abstract) Endocrine disruptors are a class of environmentally prevalent compounds that include the dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the polychlorinated biphenyls, and some isoflavonoid phytoestrogens. Their potential health hazards, until recently, were dominated by concerns over carcinogenicity following exposure of adults to high doses. Developmental toxicity now seems to be achieving a leading role and may even displace cancer as the basis for assessing the human risks posed by these compounds. One source of this shifting concern is data describing impaired sexual development in rats exposed prenatally to surprisingly low doses of TCDD. TCDD and related endocrine disrupters appear to alter the perinatal gonadal hormone milieu. Such activity triggers a cascade of disturbances in brain development and neuroendocrine function. Although such disturbances might be seen most readily in reproductive studies, a constellation of much more subtle consequences is conceivable. These outcomes might include altered gender-specific cognition. For example, female rats tend to emit different patterns of responding than male rats on schedule-controlled operant behavior assays. The current proposal is guided by the hypothesis that prenatal TCDD modifies the usual pattern of differences between male and female rats. Tests of the hypothesis will be based on three situations in which gender-specific learning, memory, and spatial cognition are assessed. One assessment situation will examine a sexually-motivated behavior in exposed females, a second situation will examine sexual motivation in exposed males, and the third situation will examine nonsexual cognitive function in both males and females. In order to determine sensitive critical periods of prenatal development, the behavioral endpoints will be examined across groups of offspring that have been exposed under one of three different prenatal schedules. All of these measures will be examined in subjects exposed to a new, low dose range of TCDD that approaches background levels in the environment. The coupling of several functional measures is adduced as a model of risk assessment.

描述：（改编自研究者摘要）内分泌 干扰物是一类环境中普遍存在的化合物，包括 二恶英，如2，3，7，8-四氯二苯并-对-二恶英（TCDD）， 多氯联苯和一些有毒植物雌激素。 他们的 直到最近，潜在的健康危害主要是担心 成年人接触高剂量的致癌性。 发育 毒性现在似乎正在发挥主导作用，甚至可能取代 癌症作为评估这些化合物对人类造成的风险的基础。 这种转变担忧的一个来源是描述性功能受损的数据。 出生前暴露于低剂量TCDD的大鼠的发育。 TCDD和相关的内分泌干扰物似乎会改变围产期性腺 激素环境。 这种活动会引发大脑中的一系列干扰 发育和神经内分泌功能。 尽管这种干扰可能 在生殖研究中最容易看到， 微妙的后果是可以想象的。 这些结果可能包括改变 性别认知 例如，雌性大鼠倾向于释放不同的 在时间控制的操作上， 行为测定 目前的建议是以假设为指导的， 产前TCDD改变了男性和女性之间通常的差异模式， 雌性大鼠 假设的检验将基于以下三种情况： 其中评估了性别特异性学习、记忆和空间认知。 一种评估情况将检查性动机行为， 暴露的女性，第二种情况将检查性动机， 第三种情况将检查非性认知 在男性和女性身上都起作用。 为了确定敏感的 产前发育的关键时期，行为终点将是 在暴露于以下条件之一的后代群体中进行了检查， 三种不同的产前计划 所有这些措施都将得到审查 暴露于新的低剂量TCDD的受试者中， 环境中的背景水平。 多个泛函的耦合 措施作为风险评估的模型。